Therapeutic potential of freeze-dried Kaempferia galanga herbal formulation in alleviating hyperglycemia in diabetic mice: an in-vivo and in-silico investigation

A never-ending search is being made for a natural remedy to cure diabetes, which is one of the biggest worldwide health concerns. Kaempferia galanga (K. galanga), an important medicinal herb, is reported to have various pharmacological effects. This study aims to conduct in-depth research on the antihyperglycemic activity of K galanga in streptozotocin (STZ)-induced diabetic mice and the mechanism by which it elicits its response. For 21 days, various dosages of freeze-dried K. galanga ethanolic extract (KGE) therapy were given intraperitoneally in STZ-induced diabetic mice. KGE at 350 mg/kg b.w. was selected as the ideal dose. Acute toxicology studies have shown that KGE is non-toxic. Protein and gene expression studies targeting various metabolic pathways show that in the diabetic mice treated with KGE, there was stimulation of AKT, inhibition of glycogen synthase kinase-3, stimulation of glucokinase (GK), and inhibition of phosphoenolpyruvate carboxykinase (PEPCK) expression. Histopathological studies show the protective effect of herbal KGE on the integrity of the mice's pancreas. Molecular docking studies was performed in which the bio-active compound ethyl-p-methoxy cinnamate (EPMC) found in KGE shows good binding energy with the target protein AKT, GSK3, insulin receptor (IR), protein-tyrosine phosphatase 1B (PTB1B), GK, and PEPCK, indicating a good binding interaction. ADMET studies also revealed that EPMC has desirable physicochemical and pharmacokinetic properties and very low toxicity (LD 50 7900 mg/kg) compared to standard metformin (LD50 680 mg/kg). Herbal KGE and EPMC show a pleiotropic therapeutic effect and may be a potent adjunct and drug, respectively, in attenuating diabetes.

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